Katoh O, Kimura A, Itoh T, Kuramoto A
Department of Internal Medicine, Hiroshima University, Japan.
Am J Hematol. 1990 Nov;35(3):145-50. doi: 10.1002/ajh.2830350302.
Platelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c-sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patients.
血小板衍生生长因子（PDGF）被认为在骨髓纤维化的发病机制中起重要作用，骨髓纤维化常发生于骨髓增殖性疾病（MPD）患者。我们采用原位杂交技术，使用人PDGF A链和B链（c-sis）的cDNA探针，检测了13例MPD患者骨髓巨核细胞中PDGF mRNA的表达水平。患者两条链的mRNA水平均显著高于对照患者，其中1例原发性血小板增多症患者和1例真性红细胞增多症患者的水平明显更高。MPD患者中A链和B链的转录本呈正相关表达。通过骨髓成纤维细胞增殖试验，我们发现1例mRNA水平高的MPD患者纯化巨核细胞中的PDGF活性与1例对照患者相似。此外，先前研究表明MPD患者循环血小板中的PDGF减少。这些结果可能提示，在某些患者中，如果假设PDGF mRNA水平与合成的蛋白质呈线性相关，那么PDGF在巨核细胞中大量合成，但有一部分释放到骨髓环境中。这可能是MPD患者发生骨髓纤维化的一种可能机制。
